The mitochondrial transport of gamma-keto isocaproic and gamma-keto-beta-methyl valeric acids are being studied, and the kinetic parameters relative to this transport are being compared with those of the branched-chain gamma-keta acid dehydrogenase(s) governing the first step in the degradation of these acids. Mitochondria from rat liver and brain are being utilized, and the potential inhibitory roles of these six-carbon branched-chain gamma-keto acids toward the transport of pyruvate and gamma-ketoglutarate are being investigated. In addition branched-chain gamma-keto acid dehydrogenase activity in human tissue obtained at autopsy is being evaluated. Preparation of pure enzyme from that tissue having highest activity will be undertaken, and the pure enzyme used for characterization studies. Kinetic parameters of this enzyme will be compared with those of the enzyme found in fibroblasts grown from the skin of patients with various forms of Maple Syrup Urine Disease; and the electrophoretic patterns of the normal and abnormal enzymes will be evaluated on polyacrylamide gels.